Diethyl N-<4-<2-(2,4-diaminopyrrolo<2,3-d>pyrimidin-5-yl)ethyl>benzoyl>-L-glutamate | 134373-07-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Diethyl N-<4-<2-(2,4-diaminopyrrolo<2,3-d>pyrimidin-5-yl)ethyl>benzoyl>-L-glutamate
• 英文别名: diethyl (2S)-2-[[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioate
• CAS: 134373-07-2
• 化学式: C₂₄H₃₀N₆O₅
• 分子量: 482.539
• InChiKey: DOOPZICZSJTGTC-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  175
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Diethyl N-<4-<2-(2,4-diaminopyrrolo<2,3-d>pyrimidin-5-yl)ethyl>benzoyl>-L-glutamate 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以92%的产率得到TNP-351
  参考文献：
  名称：

  A novel synthetic approach to pyrrolo[2,3-d]pyrimidine antifolates

  摘要：

  A novel and efficient synthetic method for the synthesis of pyrrolo[2,3-d]pyrimidine antifolates is described. The key reaction of this method is the photo-initiated free radical addition of bromomalononitrile or ethyl bromocyanoacetate to an enol ether to afford the backbone skeleton of the targeted antifolate molecule. The key intermediates 3 or 4 are smoothly converted to the pyrrolo[2,3-d]pyrimidine antifolates 1 or 2 in three steps and in high overall yield.

  DOI：

  10.1021/jo00059a016
• 作为产物：
  描述：

  Ethyl 4-<2-(2,4-diaminopyrrolo<2,3-d>pyrimidin-5-yl)ethyl>benzoate 在 N-甲基吗啉 、 sodium hydroxide 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 Diethyl N-<4-<2-(2,4-diaminopyrrolo<2,3-d>pyrimidin-5-yl)ethyl>benzoyl>-L-glutamate
  参考文献：
  名称：

  A One-Step Ring Transformation/Ring Annulation Approach to Pyrrolo[2,3-d]pyrimidines. A New Synthesis of the Potent Dihydrofolate Reductase Inhibitor TNP-351

  摘要：

  Condensation of amidines with 2-amino-3-cyanofurans gives 2-substituted-4-aminopyrrolo[2,3-d]-pyrimidines by a ring-opening, ring-recyclization sequence of reactions through which the starting furan 2-amino nitrogen becomes the pyrrole nitrogen of the final product and one of the amidine nitrogens becomes N-1 of the fused pyrimidine ring. 2,4-Diamino-5-[2-(4-carbethoxyphenyl)ethyl]- pyrrolo[2,3-d]pyrimidine, a key intermediate in the synthesis of the DHFR inhibitor TNP-351, has been prepared in one step by reaction of ethyl 4-[2-(2-amino-3-cyanofuran-4-yl)ethyl]be with guanidine.

  DOI：

  10.1021/jo00126a017

文献信息

• US5349064A
  申请人：——

  公开号：US5349064A

  公开（公告）日：1994-09-20
• US5496946A
  申请人：——

  公开号：US5496946A

  公开（公告）日：1996-03-05
• A novel synthetic approach to pyrrolo[2,3-d]pyrimidine antifolates
  作者：Tetsuo Miwa、Takenori Hitaka、Hiroshi Akimoto

  DOI：10.1021/jo00059a016

  日期：1993.3

  A novel and efficient synthetic method for the synthesis of pyrrolo[2,3-d]pyrimidine antifolates is described. The key reaction of this method is the photo-initiated free radical addition of bromomalononitrile or ethyl bromocyanoacetate to an enol ether to afford the backbone skeleton of the targeted antifolate molecule. The key intermediates 3 or 4 are smoothly converted to the pyrrolo[2,3-d]pyrimidine antifolates 1 or 2 in three steps and in high overall yield.
• A One-Step Ring Transformation/Ring Annulation Approach to Pyrrolo[2,3-d]pyrimidines. A New Synthesis of the Potent Dihydrofolate Reductase Inhibitor TNP-351
  作者：Edward C. Taylor、Hemantkumar H. Patel、Jong-Gab Jun

  DOI：10.1021/jo00126a017

  日期：1995.10

  Condensation of amidines with 2-amino-3-cyanofurans gives 2-substituted-4-aminopyrrolo[2,3-d]-pyrimidines by a ring-opening, ring-recyclization sequence of reactions through which the starting furan 2-amino nitrogen becomes the pyrrole nitrogen of the final product and one of the amidine nitrogens becomes N-1 of the fused pyrimidine ring. 2,4-Diamino-5-[2-(4-carbethoxyphenyl)ethyl]- pyrrolo[2,3-d]pyrimidine, a key intermediate in the synthesis of the DHFR inhibitor TNP-351, has been prepared in one step by reaction of ethyl 4-[2-(2-amino-3-cyanofuran-4-yl)ethyl]be with guanidine.